The broad objective of this program concerns methodological aspects of clinical evaluation in the psychopharmacological treatment of anxiety and depression. Symptomatic volunteers and neurotic outpatients are used as subjects in single-dose and chronic drug trials investigating the effects of drugs upon human behavior. Experimental models of anxiety and depression are studied to determine their usefulness in predicting clinical response to pharmacotherapy. Of particular interest are problems relating to placebo response and interactions between subject characteristics, experimental settings, and drug action.